Fumitaka Yanase1,2, Tomoko Fujii2,3, Thummaporn Naorungroj1,4, Alessandro Belletti1,5, Nora Luethi2,6, Anitra C Carr7, Paul J Young8,9, Rinaldo Bellomo1,2,10. 1. Department of Intensive Care, Austin Hospital, Heidelberg, VIC, Australia. 2. Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, VIC, Australia. 3. Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine, Kyoto, Japan. 4. Department of Intensive Care, Siriraj Hospital, Mahidol University, Bangkok, Thailand. 5. Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy. 6. Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland. 7. Nutrition in Medicine Research Group, Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand. 8. Intensive Care Unit, Wellington Hospital, Wellington, New Zealand. 9. Medical Research Institute of New Zealand, Wellington, New Zealand. 10. Centre for Integrated Critical Care, Department of Medicine & Radiology, University of Melbourne, Melbourne, VIC, Australia.
Abstract
OBJECTIVES: The potential harm associated with the use of IV vitamin C has not been systematically assessed. We aimed to review the available evidence on harm related to such treatment. DATA SOURCES: We searched MEDLINE, EMBASE, Cochrane Library, National Institute of Health Clinical Trials Register, and World Health Organization International Clinical Trials Registry Platform. STUDY SELECTION: We included studies in adult population that reported harm related to IV high-dose vitamin C which we defined as greater than or equal to 6 g/d, greater than or equal to 75 mg/kg/d, or greater than or equal to 3 g/m/d. DATA EXTRACTION: Two independent investigators screened records and extracted data. DATA SYNTHESIS: We identified 8,149 reports, of which 650 full text were assessed for eligibility, leaving 74 eligible studies. In these studies, 2,801 participants received high-dose vitamin C at a median (interquartile range) dose of 22.5 g/d (8.25-63.75 g/d), 455 mg/kg/d (260-925 mg/kg/d), or 70 g/m/d (50-90 g/m/d); and 932 or more adverse events were reported. Among nine double-blind randomized controlled trials (2,310 patients), adverse events were reported in three studies with an event rate per patient for high-dose vitamin C identical to placebo group in one study (0.1 [1/10] vs 0.1 [1/10]), numerically lower in one study (0.80 [672/839] vs 0.82 [709/869]), and numerically higher in one study (0.33 [24/73] vs 0.23 [17/74]). Six double-blind randomized controlled trials reported no adverse event in either group. Five cases of oxalate nephropathy, five cases of hypernatremia, three cases of hemolysis in glucose-6-phosphate dehydrogenase deficiency patients, two cases of glucometer error, and one case of kidney stones were also reported overall. CONCLUSIONS: There is no consistent evidence that IV high-dose vitamin C therapy is more harmful than placebo in double-blind randomized controlled trials. However, reports of oxalate nephropathy, hypernatremia, glucometer error, and hemolysis in glucose-6-phosphate dehydrogenase deficiency patients warrant specific monitoring.
OBJECTIVES: The potential harm associated with the use of IV vitamin C has not been systematically assessed. We aimed to review the available evidence on harm related to such treatment. DATA SOURCES: We searched MEDLINE, EMBASE, Cochrane Library, National Institute of Health Clinical Trials Register, and World Health Organization International Clinical Trials Registry Platform. STUDY SELECTION: We included studies in adult population that reported harm related to IV high-dose vitamin C which we defined as greater than or equal to 6 g/d, greater than or equal to 75 mg/kg/d, or greater than or equal to 3 g/m/d. DATA EXTRACTION: Two independent investigators screened records and extracted data. DATA SYNTHESIS: We identified 8,149 reports, of which 650 full text were assessed for eligibility, leaving 74 eligible studies. In these studies, 2,801 participants received high-dose vitamin C at a median (interquartile range) dose of 22.5 g/d (8.25-63.75 g/d), 455 mg/kg/d (260-925 mg/kg/d), or 70 g/m/d (50-90 g/m/d); and 932 or more adverse events were reported. Among nine double-blind randomized controlled trials (2,310 patients), adverse events were reported in three studies with an event rate per patient for high-dose vitamin C identical to placebo group in one study (0.1 [1/10] vs 0.1 [1/10]), numerically lower in one study (0.80 [672/839] vs 0.82 [709/869]), and numerically higher in one study (0.33 [24/73] vs 0.23 [17/74]). Six double-blind randomized controlled trials reported no adverse event in either group. Five cases of oxalatenephropathy, five cases of hypernatremia, three cases of hemolysis in glucose-6-phosphate dehydrogenase deficiencypatients, two cases of glucometer error, and one case of kidney stones were also reported overall. CONCLUSIONS: There is no consistent evidence that IV high-dose vitamin C therapy is more harmful than placebo in double-blind randomized controlled trials. However, reports of oxalatenephropathy, hypernatremia, glucometer error, and hemolysis in glucose-6-phosphate dehydrogenase deficiencypatients warrant specific monitoring.
Authors: Patrick M Honore; Sydney Blackman; Ibrahim Bousbiat; Emily Perriens; Rachid Attou Journal: Clin Pharmacokinet Date: 2022-07-30 Impact factor: 5.577
Authors: Yugeesh R Lankadeva; Rachel M Peiris; Nobuki Okazaki; Ian E Birchall; Anton Trask-Marino; Anthony Dornom; Tom A M Vale; Roger G Evans; Fumitaka Yanase; Rinaldo Bellomo; Clive N May Journal: Crit Care Med Date: 2021-02-01 Impact factor: 9.296